Significance Disorders of kidney development represent a major cause of renal failure and end stage renal disease in the pediatric population. Although congenital obstructive nephropathy is a major cause of chronic renal failure, little progress has been made towards understanding pathophysiologic mechanism(s) and developing methods for prevention and treatment. Objectives In order to further our understanding of the prenatal pathogenesis of renal dysplasia, develop markers to predict postnatal compromise, and design interventive strategies for improving the outcome of obstructive nephropathy and renal dysplasia, a fetal monkey model that closely parallels human development is being studied. Results An ultrasound-guided technique was used for inducing unilateral ureteral obstruction in the fetal monkey during the early second trimester. There was no evidence of oligohydramnios, and the obstructed kidneys were progressively smaller than the contralateral (non-obstructed) kidneys when monitored sonographically over time. Generally, fetuses showed all the classic histopathologic features of human renal dysplasia. The obstructed kidneys contained numerous cortical cysts of various sizes which appeared to be derived from all segments of the nephron including the collecting duct and glomeruli. Some of the cortical cysts were surrounded by a smooth muscle collar, characteristic of renal dysplasia. In the medulla, the larger collecting ducts were dilated and smooth muscle actin immunoreactivity demonstrated the presence of periductular smooth muscle collars. The medullary interstitium also appeared abnormal, with an expanded stroma highlighted by vimentin immunoreactivity. Other features included the presence of detached cells in the lumen of the cysts, and cells within the epithelial lining of the cysts which appeared grossly apoptotic. The contralateral kidneys were all normal. Future Directions We are currently localizing and characterizing apoptosis in both obstructed and non-obstructed kidneys, and defining the role of the insulin-like growth factor (IGF) system in obstructive nephropathy and renal disease. KEY WORDS fetus, kidney, IGF system, apoptosis, obstructive uropathy FUNDING NIH Grant DK53711